Maastricht Univ. Medical Centre, Cardiovascular Research Institute Maastricht, Maastricht, The Netherlands.
Am J Physiol Endocrinol Metab. 2012 Mar 1;302(5):E481-95. doi: 10.1152/ajpendo.00540.2011. Epub 2011 Dec 13.
Endothelial nitric oxide synthase (eNOS) serves as a critical enzyme in maintaining vascular pressure by producing nitric oxide (NO); hence, it has a crucial role in the regulation of endothelial function. The bioavailability of eNOS-derived NO is crucial for this function and might be affected at multiple levels. Uncoupling of eNOS, with subsequently less NO and more superoxide generation, is one of the major underlying causes of endothelial dysfunction found in atherosclerosis, diabetes, hypertension, cigarette smoking, hyperhomocysteinemia, and ischemia/reperfusion injury. Therefore, modulating eNOS uncoupling by stabilizing eNOS activity, enhancing its substrate, cofactors, and transcription, and reversing uncoupled eNOS are attractive therapeutic approaches to improve endothelial function. This review provides an extensive overview of the important role of eNOS uncoupling in the pathogenesis of endothelial dysfunction and the potential therapeutic interventions to modulate eNOS for tackling endothelial dysfunction.
内皮型一氧化氮合酶（eNOS）通过产生一氧化氮（NO）来维持血管压力，因此在调节内皮功能方面起着至关重要的作用。eNOS 衍生的 NO 的生物利用度对于这一功能至关重要，并且可能在多个层面受到影响。eNOS 的解偶联，随之而来的是 NO 生成减少和超氧化物生成增加，是动脉粥样硬化、糖尿病、高血压、吸烟、高同型半胱氨酸血症和缺血/再灌注损伤中发现的内皮功能障碍的主要潜在原因之一。因此，通过稳定 eNOS 活性、增强其底物、辅助因子和转录以及逆转解偶联的 eNOS 来调节 eNOS 解偶联，是改善内皮功能的一种有吸引力的治疗方法。本综述广泛概述了 eNOS 解偶联在内皮功能障碍发病机制中的重要作用，以及调节 eNOS 以解决内皮功能障碍的潜在治疗干预措施。
